Poxviruses, which include variola major (VARV), vaccinia virus (VACV), monkeypox, ectromelia virus (ECTV) and others, belong to the orthopoxvirus genus. Poxviruses are large, complex viruses. A poxvirus genome encodes about 200 proteins. The complexity of poxviruses has, in part, delayed the identification of protective antigens. On the other hand, considerable cross-protection has been observed between orthopox viruses. For example, vaccination with live attenuated vaccinia virus protects from infection by variola major, the virus that causes smallpox. The original smallpox vaccine, based on live attenuated vaccinia, eradicated smallpox from the worldwide human population with the last case of natural smallpox infection occurring in Somalia in 1977 (Radetsky, 1999, Pediat. Inf. Dis. J., 18:85-93). Production of the live, attenuated vaccinia approved for use as a smallpox vaccine in the United States, DryVax™ (Wyeth Laboratories, Inc.) was discontinued in 1982. Adverse events associated with vaccination with the live attenuated virus vaccine include progressive vaccinia, eczema, post-vaccinial encephalitis, and myocarditis (Casey et al., 2005, JAMA, 294(21):2734-43; Belongia et al., 2003, Clin. Med. Res., 1(2):87-92). Despite safety concerns, live vaccinia virus remains the main form of smallpox vaccine. A new generation of live attenuated vaccinia virus vaccines are being produced in cultured cells for stockpiling in hopes that the supply will be available to protect the general population in the event of a bioterrorist attack, as the majority of the world's population no longer has immunity to smallpox (Artenstein et al., 2005, Vaccine, 23(25):3301-9; Fang et al., 2006, Virology 345(1):231-43; Monath et al., 2004, Int. J. Infect. Dis., 8 (Suppl 2):S31-44).